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Platelets Fuel The Inflammasome Activation Of Innate Immune Cells, Verena Rolfes, Lucas Secchim Ribeiro, Eicke Latz, Moshe Arditi, Bernardo Simoes Franklin 2020 University of Bonn

Platelets Fuel The Inflammasome Activation Of Innate Immune Cells, Verena Rolfes, Lucas Secchim Ribeiro, Eicke Latz, Moshe Arditi, Bernardo Simoes Franklin

Open Access Articles

The inflammasomes control the bioactivity of pro-inflammatory cytokines of the interleukin (IL)-1 family. The inflammasome assembled by NLRP3 has been predominantly studied in homogeneous cell populations in vitro, neglecting the influence of cellular interactions that occur in vivo. Here, we show that platelets boost the inflammasome capacity of human macrophages and neutrophils and are critical for IL-1 production by monocytes. Platelets license NLRP3 transcription, thereby enhancing ASC oligomerization, caspase-1 activity, and IL-1beta secretion. Platelets influence IL-1beta production in vivo, and blood platelet counts correlate with plasmatic IL-1beta levels in malaria. Furthermore, we reveal an enriched platelet gene signature among ...


The Development And Evaluation Of Alginate Nanofibers As A Neuroprotective Nano-Scaffold For Amyotrophic Lateral Sclerosis (Als), Julia Bielanin 2020 University of Arkansas, Fayetteville

The Development And Evaluation Of Alginate Nanofibers As A Neuroprotective Nano-Scaffold For Amyotrophic Lateral Sclerosis (Als), Julia Bielanin

Chemistry & Biochemistry Undergraduate Honors Theses

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disorder characterized in pathology by a significant loss of upper and lower motor neurons, leading to muscle wasting and loss of voluntary movement. There are about 6,000-8,000 new cases of ALS diagnosed per year in the U.S., with a fatal outcome within 2 to 4 years (on average) after diagnosis. There are only two FDA approved drugs for treating ALS. Both are very expensive and only have modest benefits for patients. The population is in dire need of more affordable and effective medicine for the treatment of ALS ...


Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent 2019 University of Louisville

Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent

Electronic Theses and Dissertations

This thesis describes the development of a novel lectin-Fc fusion protein and its antiviral and anti-cancer activity. The molecule, Avaren-Fc (AvFc), is a fusion of a variant of the actinomycete lectin actinohivin (Avaren) and the Fc region of human IgG1, and is selective for the terminal α1,2-mannose residues found at the ends of high-mannose-type glycans that can be found on the surface of certain heavily glycosylated viruses and cancer cells. Here, AvFc was found to be able to neutralize simian immunodeficiency virus as well as Hepatitis C virus with nanomolar IC50 values. Furthermore, AvFc recognizes a number of ...


The First In Vivo Human Methionine Sulfide Proteome And The Impact Of Smoking, Abdullah Qassab 2018 University of Arkansas, Fayetteville

The First In Vivo Human Methionine Sulfide Proteome And The Impact Of Smoking, Abdullah Qassab

Theses and Dissertations

Reactive oxygen species are naturally generated within the human body and they are known to modulate signaling pathway and mediate other physiological activities. However, excessive generation of ROS and the inability of body defense system in detoxifying them results in the so called “oxidative stress”. Methionine has powerful antioxidant properties due to the presence of electronegative sulfur in its structure. Therefore, Met is readily oxidized, and methionine sulfoxide has been linked to several pathological conditions.

The urinary proteome is an attractive candidate for the discovery of biomarkers to diagnose and classify health conditions because of the non-invasive collection procedure. However ...


Design And Development Of A Quartz Crystal Microbalance Immunosensor For Exosomes, Wesley Cox 2018 University of Tennessee, Knoxville

Design And Development Of A Quartz Crystal Microbalance Immunosensor For Exosomes, Wesley Cox

Chancellor’s Honors Program Projects

No abstract provided.


Towards An Arthritis Flare-Responsive Drug Delivery System, Nitin Joshi, Ellen M. Gravallese, Joerg Ermann, Jeffrey M. Karp 2018 Massachusetts Institute of Technology

Towards An Arthritis Flare-Responsive Drug Delivery System, Nitin Joshi, Ellen M. Gravallese, Joerg Ermann, Jeffrey M. Karp

Open Access Articles

Local delivery of therapeutics for the treatment of inflammatory arthritis (IA) is limited by short intra-articular half-lives. Since IA severity often fluctuates over time, a local drug delivery method that titrates drug release to arthritis activity would represent an attractive paradigm in IA therapy. Here we report the development of a hydrogel platform that exhibits disassembly and drug release controlled by the concentration of enzymes expressed during arthritis flares. In vitro, hydrogel loaded with triamcinolone acetonide (TA) releases drug on-demand upon exposure to enzymes or synovial fluid from patients with rheumatoid arthritis. In arthritic mice, hydrogel loaded with a fluorescent ...


Enhancing Clot Properties Through Fibrin-Specific Self-Cross-Linked Peg Side-Chain Microgels, Nicole Welsch, Ashley C. Brown, Thomas H. Barker, L. Andrew Lyon 2018 Georgia Institute of Technology

Enhancing Clot Properties Through Fibrin-Specific Self-Cross-Linked Peg Side-Chain Microgels, Nicole Welsch, Ashley C. Brown, Thomas H. Barker, L. Andrew Lyon

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Excessive bleeding and resulting complications are a major cause of death in both trauma and surgical settings. Recently, there have been a number of investigations into the design of synthetic hemostatic agents with platelet-mimicking activity to effectively treat patients suffering from severe hemorrhage. We developed platelet-like particles from microgels composed of polymers carrying polyethylene glycol (PEG) side-chains and fibrin-targeting single domain variable fragment antibodies (PEG-PLPs). Comparable to natural platelets, PEG-PLPs were found to enhance the fibrin network formation in vitro through strong adhesion to the emerging fibrin clot and physical, non-covalent cross-linking of nascent fibrin fibers. Furthermore, the mechanical reinforcement ...


Development And Preclinical Evaluation Of Long-Lasting Cocaine Hydrolases For Cocaine Overdose And Cocaine Use Disorder Treatment, Ting Zhang 2018 University of Kentucky

Development And Preclinical Evaluation Of Long-Lasting Cocaine Hydrolases For Cocaine Overdose And Cocaine Use Disorder Treatment, Ting Zhang

Theses and Dissertations--Pharmacy

Cocaine is a plant-based illicit drug commonly involved in substance use disorder. Although cocaine overdose and cocaine use disorders cause adverse health consequences to individuals and the economic burden on their family and society, there are no FDA (Food and Drug Administration) approved medications for treatment. Recently, it has been recognized that delivery of cocaine hydrolase (CocH) is a promising therapeutic strategy. Human butyrylcholinesterase (hBChE), the primary enzyme involved in cocaine metabolism in human, have advantages over other candidates for the development of CocH. Previous studies in our laboratory have designed and characterized hBChE mutants that have ~4,000-fold improved ...


Cannabinoid Receptor 2 And C-X-C Chemokine Receptor 4 Interact To Abrogate Cxcl12-Mediated Cellular Response, Christopher James Coke 2017 Atlanta University Center

Cannabinoid Receptor 2 And C-X-C Chemokine Receptor 4 Interact To Abrogate Cxcl12-Mediated Cellular Response, Christopher James Coke

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The expression of C-X-C Chemokine Receptor 4 (CXCR4) has been correlated with increased metastatic potential of cancer cells. CXCR4 increases tumor malignancy by encouraging tumors cells to migrate to distal organs expressing its cognate ligand, CXCL12, facilitating metastasis. Thus, targeting the CXCR4/CXCL12 signaling axis provides a good strategy to inhibit the metastatic spread of tumor cells and slow cancer progression. Various studies suggest that cannabis may have anti-proliferative as well as anti-metastatic properties, though a biochemical mechanism describing how this occurs has yet to be discovered. Our lab has confirmed that agonist-bound CXCR4 and agonist-bound Cannabinoid Receptor 2 (CB2 ...


Diversity Oriented Synthesis, Characterization And Anti-Cancer Activity Of Killer Peptide Nucleolipid Bioconjugates, Niki K. Rana 2017 Seton Hall University

Diversity Oriented Synthesis, Characterization And Anti-Cancer Activity Of Killer Peptide Nucleolipid Bioconjugates, Niki K. Rana

Seton Hall University Dissertations and Theses (ETDs)

The killer peptide sequence D-(KLAKLAK)2 has been originally designed and developed as an antibacterial agent. Despite having excellent cytotoxicity towards bacteria, this sequence maintains low cell cytotoxity in malignant mammalian cell types such as cancer. The chemical basis for its selectivity has been attributed to its poly(cationic) amphiphilic nature, which facilitates cell permeability across the negatively charged bacterial membrane, but with limited permeability across the zwitterionic membrane of mammalian cells. The positively charged D-(KLAKLAK)2 sequence has been found to accumulate on the surface of the mitochondria causing dissipation of the negatively charged mitochondrial membrane potential ...


Shape Recovery With Concomitant Mechanical Strengthening Of Amphiphilic Shape Memory Polymers In Warm Water, Ben Zhang, Janae E. DeBartolo, Jie Song 2017 University of Massachusetts Medical School

Shape Recovery With Concomitant Mechanical Strengthening Of Amphiphilic Shape Memory Polymers In Warm Water, Ben Zhang, Janae E. Debartolo, Jie Song

University of Massachusetts Medical School Faculty Publications

Maintaining adequate or enhancing mechanical properties of shape memory polymers (SMPs) after shape recovery in an aqueous environment are greatly desired for biomedical applications of SMPs as self-fitting tissue scaffolds or minimally invasive surgical implants. Here we report stable temporary shape fixing and facile shape recovery of biodegradable triblock amphiphilic SMPs containing a poly(ethylene glycol) (PEG) center block and flanking poly(lactic acid) or poly(lactic-co-glycolic acid) blocks in warm water, accompanied by concomitant enhanced mechanical strengths. Differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WXRD), and small-angle X-ray scattering (SAXS) analyses revealed that the unique stiffening of the amphiphilic ...


A Diversity-Oriented Synthesis Approach To Functionalized Azaheterocycles Using Cyclic Alpha-Halo Eneformamides, Spencer A. Langevin 2017 Central Washington University

A Diversity-Oriented Synthesis Approach To Functionalized Azaheterocycles Using Cyclic Alpha-Halo Eneformamides, Spencer A. Langevin

All Master's Theses

Functionalized piperidines, azepanes, azamacrocycles, morpholines, and thiomorpholines are common structural motifs found in a wide range of pharmaceuticals such as carmegliptine, levofloxacin, thioridazine, claviciptic acid, and azithomycin. As a result, there is a strong desire to construct highly functionalized nitrogen-bearing ring scaffolds in order to construct a wide range of drug possibilities. There are several non-modular and step-uneconomical synthetic methods used in the construction of these aforementioned motifs such as ring closing metathesis, ring expansions, and intramolecular reductive amination. In this research, we present a step-economical, cost-effective, scalable, and diversity-oriented synthesis approach to highly functionalized N-heterocycles through the intermediacy of ...


Recent Insights Into The Molecular Mechanisms Of The Nlrp3 Inflammasome Activation, Tomasz Prochnicki, Matthew S. Mangan, Eicke Latz 2016 University of Bonn

Recent Insights Into The Molecular Mechanisms Of The Nlrp3 Inflammasome Activation, Tomasz Prochnicki, Matthew S. Mangan, Eicke Latz

Open Access Articles

Inflammasomes are high-molecular-weight protein complexes that are formed in the cytosolic compartment in response to danger- or pathogen-associated molecular patterns. These complexes enable activation of an inflammatory protease caspase-1, leading to a cell death process called pyroptosis and to proteolytic cleavage and release of pro-inflammatory cytokines interleukin (IL)-1beta and IL-18. Along with caspase-1, inflammasome components include an adaptor protein, ASC, and a sensor protein, which triggers the inflammasome assembly in response to a danger signal. The inflammasome sensor proteins are pattern recognition receptors belonging either to the NOD-like receptor (NLR) or to the AIM2-like receptor family. While the molecular ...


Synthesis Of Β-Triphosphotriester Pronucleotides, Yousef A. Beni, Chandravanu Dash, Keykavous Parang 2015 Tennessee State University

Synthesis Of Β-Triphosphotriester Pronucleotides, Yousef A. Beni, Chandravanu Dash, Keykavous Parang

Pharmacy Faculty Articles and Research

Dinucleoside phosphorochloridite were synthesized from phosphorus trichloride and three nucleoside analogues, 3-fluoro-2,3-dideoxythymidine (FLT), 2',3'-dideoxy-5-fluoro-3'- thiacytidine (FTC), and 2',3'-dideoxy-3'-thiacytidine (3TC), in a multistep synthesis. Polymerbound N-Boc p-acetoxybenzyl 5¢-O-2¢-deoxythymidine was reacted with dinucleoside phosphorochloridite in the presence of 2,6-lutidine, followed by the reaction with dodecyl alcohol and 5-(ethylthio)-1H-tetrazole, oxidation with tert-butyl hydroperoxide, and acidic cleavage, respectively, to afford the b-triphosphotriester derivatives containing three different nucleosides.


Poly(Ester Amide) And Poly(Ethyl Glyoxylate) Nanoparticles For Controlled Drug Release, Amira Mohamed Moustafa 2014 The University of Western Ontario

Poly(Ester Amide) And Poly(Ethyl Glyoxylate) Nanoparticles For Controlled Drug Release, Amira Mohamed Moustafa

Electronic Thesis and Dissertation Repository

The objective of this research was to develop polymeric nanoparticles (NPs) having improved drug release properties for drug delivery. Poly(ester amide)s (PEAs) are promising biodegradable polymers. PEA NPs were prepared via emulsification-evaporation and salting-out methods and optimized through by varying different processing parameters. Polymer-model drug conjugates based on PEAs containing L-aspartic acid and rhodamine B were synthesized and used for NP preparation. Release behavior was studied and compared to a control system with physically encapsulated rhodamine B. It was shown that the release of rhodamine B from the covalent system did not show the burst effect and exhibited ...


Quantifying The Effect Of A Novel Topical Hyaluronic-Acid Phosphatidylethanolamine Cream On The Epidermis, Caitlin J. Symonette 2014 The University of Western Ontario

Quantifying The Effect Of A Novel Topical Hyaluronic-Acid Phosphatidylethanolamine Cream On The Epidermis, Caitlin J. Symonette

Electronic Thesis and Dissertation Repository

With aging, keratinocytes have diminished proliferative capacity resulting in atrophic skin with reduced barrier function. This investigation evaluates the effect of daily topical applications of a novel high-molecular weight hyaluronan cream (HA-PE) on keratinocyte renewal and epidermal thickness. Unmodified hyaluronan and HA-PE were mixed separately into a vehicle cream. Each topical formulation was applied daily onto the shaved backs of aged female C57BL6 mice. Full-thickness biopsies of treated skin were obtained for analysis of keratinocyte proliferation, keratinocyte differentiation, and local inflammation at days 1, 5, and 10 of cream application. In addition, a cardiac puncture was performed for serum C-reactive ...


Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres 2014 University of Massachusetts - Amherst

Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres

Doctoral Dissertations

Proteins have the capacity to bind specific sets of compounds known as ligands, these are small molecules with a recurrent theme in their molecular design that is a characteristic exploited here to (i) identify particular affinities of small molecules for proteins with the aim of using them as ligands, inhibitors, or targeting moieties in more complex systems by means of a methodology that screens small molecules based on protein affinity; (ii) decorate a self-assembling supramolecular system at different positions, making it responsive to a complementary protein with the aim of exploring differences in disassembly and sensitivity of the release of ...


Development Of Non-Covalent Functionalization Of Carbon Nanotubes For Sirna Delivery, King Sun Siu 2014 The University of Western Ontario

Development Of Non-Covalent Functionalization Of Carbon Nanotubes For Sirna Delivery, King Sun Siu

Electronic Thesis and Dissertation Repository

RNA interference (RNAi) therapy is promising for treating various diseases but the delivery of small interfering RNA (siRNA) is difficult. To overcome the technical difficulties of siRNA delivery, an efficient and targeted delivery of siRNA is required for efficient RNAi therapy. Single-walled carbon nanotubes (CNT) has been used for nucleic acid delivery such as siRNA delivery. It has been found that CNT can gain entry into the cells by a diffusion-like mechanism which was called “nano-needle”. However, the solubility of CNT is low in most of the solvents including water. Functionalization of CNT can be carried out to enhance the ...


Anti-Chaperone Activity And Cytotoxicity Of Chemical Components In Copaiba Oil, Daniel Kulman, Janine Naim, Bin Su Ph.D. 2013 Cleveland State University

Anti-Chaperone Activity And Cytotoxicity Of Chemical Components In Copaiba Oil, Daniel Kulman, Janine Naim, Bin Su Ph.D.

Undergraduate Research Posters 2013

Copaiba oil derived from the oleoresin of the Copaiba tree has been widely used as an antiseptic and expectorant for the respiratory tract, and as anti-inflammatory agent in various skin diseases. Studies have indicated that Copaiba oil exhibited anti-carcinogenic properties in various preclinical studies. However, the anti-cancer mechanisms of copaiba oil still remain unclear. There are various diterpenoid compounds within Copaiba oil, which also make the mechanism investigation very difficult. Hardwickiic acid (HAA), a clerodane diterpenoid isolated from Copaiba oil shows anti-chaperone activity from a recent study. In the current study, cytotoxicity and anti-chaperone assay guided isolation led to 9 ...


Folate Receptor-Targeting Liposomes For The Delivery Of Antisense Molecules To Cancer Cells, Colin J. Way 2013 The University of Western Ontario

Folate Receptor-Targeting Liposomes For The Delivery Of Antisense Molecules To Cancer Cells, Colin J. Way

Electronic Thesis and Dissertation Repository

RNAi (RNA interference) is emerging as a promising tool for cancer therapy. Small interfering RNA (siRNA) molecules are activated in that pathway to reduce specific tumour cell RNAs that mediate malignancy. SiRNA treatment has been primarily limited to in vitro studies: lack of efficient, preferential in vivo delivery to target cells remains a major obstacle. Many human tumours overexpress folate receptors (FR), and siRNA-mediated reduction of thymidylate synthase (TS) sensitizes tumour cells to anti-TS drugs. I developed a folate-containing cationic liposome to preferentially deliver anti-TS siRNA to FR-expressing human tumour cells. I show, in vitro, that liposome-encapsulated siRNA (but not ...


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